Le coeur des ARN non codants - Un long chemin à découvrir [In the heart of noncoding RNA: a long way to go].

The identification and characterization of long noncoding RNA in a variety of tissues represent major achievements that contribute to our understanding of the molecular mechanisms controlling gene expression. In particular, long noncoding RNA play crucial roles in the epigenetic regulation of the adaptive response to environmental cues via their capacity to target chromatin modifiers to specific locus. In addition, these transcripts have been implicated in controlling splicing, translation and degradation of messenger RNA. Long noncoding RNA have also been shown to act as decoy molecules for microRNA. In the heart, a few long noncoding RNA have been demonstrated to regulate cardiac commitment and differentiation during development. Furthermore, recent findings suggest their involvement as regulators of the pathophysiological response to injury in the adult heart. Their high cellular specificity makes them attractive target molecules for innovative therapies and ideal biomarkers

The promise of enhancer-associated long noncoding RNAs in cardiac regeneration.

Heart failure is a worldwide epidemic and represents a major cause of morbidity and mortality. Current clinical therapies for heart disease prolong survival by protecting the viable muscle, but they are unable to replenish lost cardiomyocytes to restore function. Over the last decade, the notion of promoting cardiac regeneration has engendered considerable research interest. New strategies envisage the transfer of stem cells into the damaged myocardium, the mobilization of cardiac precursor cells, the promotion of cardiomyocyte proliferation in situ and direct reprogramming of non-cardiac cells into electromechanically coupled cardiomyocytes. The molecular and cellular mechanisms underpinning these different regenerative avenues are under the control of integrated transcriptional programs, which are ultimately dependent on epigenomic reprogramming and reorganization of the genome nuclear architecture. Today, it is becoming evident that regulatory noncoding RNAs play fundamental roles in all these aspects of gene regulatory network activity. In particular, thousands of long noncoding RNAs are dynamically expressed across the entire genome during lineage-specific commitment, specialization, and differentiation, as well as during the response to environmental cues. Here, we review this emerging landscape, focusing particularly on a unique class of lncRNA emerging from enhancer sequences, the enhancer-associated lncRNAs, in the context of cardiac regeneration. We propose that characterizing and manipulating these enhancer-associated transcripts could provide a novel approach to awaken the dormant regenerative potential of the adult mammalian heart. Ultimately, this could lead to targeted noncoding RNA-based enhancer therapies to improve effectiveness of current regenerative strategies and provide new avenues for repair

New Lncs to mesendoderm specification.

Mammalian genomes are pervasively transcribed generating thousands of long noncoding RNAs (lncRNAs) with emergent regulatory roles. Many of these lncRNAs exhibit highly specialised expression patterns during development and typically flank and regulate key developmental factors. In this review, we discuss and summarise the latest advances in our understanding of the roles of lncRNAs during mesendoderm (ME) specification, a key step during gastrulation and the formation of the primitive streak (PS)

MODULAR APPROACH TO CHIRAL PYRIDINE CONTAINING MACROCYCLES: SYNTHESIS, CHARACTERIZATION, REACTIVITY AND CATALYTIC ACTIVITY OF THEIR METAL COMPLEXES

In this thesis is reported a simple, fast, economic modular approach for the synthesis of chiral tetraaza-macrocycles containing a pyridine ring (Pc-L*) starting from aminoacids. The characterization of the ligands and of their complexes with copper (I) and silver (I) salts also descrive, including several crystal suitable for X-ray determination. The organometallic reactivity and coordination behavior of these complexes with CO and acetonitrile has been studied. The complexes were succesfully applied as catalysts for cyclopropanation and A3-coupling reaction and for the synthesis of isochromenes starting from propargyl-aldehydes. In any case, excellent results in terms of yields and chemoselectivity were obtained and, concerning the cyclopropanation reaction, very good enantioselectivities on different substrates were achieved. Furthermore, a new class of Pc-L* ligands potentially dianionic is described and the complexation studies of these macrocycles with ruthenium, cobalt, zyrconium and iron are reported

Discovery and functional characterization of cardiovascular long noncoding RNAs

Recent advances in sequencing and genomic technologies have resulted in the discovery of thousands of previously unannotated long noncoding RNAs (lncRNAs). However, their function in the cardiovascular system remains elusive. Here we review and discuss considerations for cardiovascular lncRNA discovery, annotation and functional characterization. Although we primarily focus on the heart, the proposed pipeline should foster functional and mechanistic exploration of these transcripts in various cardiovascular pathologies. Moreover, these insights could ultimately lead to novel therapeutic approaches targeting lncRNAs for the amelioration of cardiovascular diseases including heart failure

Exploring high temperature magnetic order in CeTi_1-xSc_xGe

Most of magnetic transitions related to Ce ordering are found below T_ord~12K. Among the few cases exceeding that temperature, two types of behaviors can be distinguished. One of them is related to the rare cases of Ce binary compounds formed in BCC structures, with a quartet ground state, whose degeneracy is reduced by undergoing different types of transitions mostly structural. The other group shows evidences of itinerant character with the outstanding example of CeRh_3B_2 showing the highest T_ord=115K. The second highest ordering temperature has been reported for CeScGe with T_ord=47K, but the nature of this magnetic state has not been investigated very deeply. In order to shed more light into this unusual high temperature ordering we studied the structural, magnetic, transport and thermal properties of CeTi_1-xSc_xGe alloys in the stability range of the CeScSi-type structure 0.25<x<1 This system presents a rich variety of magnetic behaviors along this concentration range, with the magnetic ordering growing from ferromagnetic (FM) T_C~7K up to an antiferromagnetic (AFM) transition at T_N=47K. The different regions show the following characteristics: i) on the Ti rich side (0.25<x<0.50) it exhibits a FM ground state (GS) with large saturation magnetization values M_sat up to ~1.15 mu_B. ii) Around x=0.60, the first crystal electric field excited doublet starts to contribute to the GS magnetic properties. Furthermore an AFM component with a connected metamagnetic transition appears. iii) At x=0.65 a clear change in the GS nature is associated to a critical point above which the GS properties can be described like for an itinerant system (with decreasing M_sat) and an effective GS degeneracy N_eff=4. iv) For x>0.65, the magnetic phase boundary splits into two transitions, with an intermediate phase presenting incommensurate spin density waves features.Comment: 8 pages, 10 figure

Application in asymmetric cyclopropanation of new chiral macrocycles

Our group has been focusing for years on the synthesis and on the study of chiral macrocyclic ligand. Their complexes with metal ions \u2013 specially copper(I) and silver(I) \u2013 are competent catalysts in various organic reactions. The synthesis of this class of compounds is simple and fast (scheme 1). It does not involve either complex procedures nor expensive reagents, since the macrocycles can be obtained from enantiomerically pure and naturally available aminoacids in good yields (overall 40-50%). In this presentation, we reported the synthesis of three new chiral ligands bearing different chiral arms on the macrocyclic backbone. We also report the studies of complexation of these ligands by Ag(I) and Cu(I) ions and the good applicative results of the latter complexes as catalysts for the cyclopropanation reaction of \u3b1-methylstyrene